Pharmacokinetics of melphalan in children following high-dose intravenous injection.

The pharmacokinetics of high-dose IV melphalan (140 or 220 mg m-2) were studied after 12 administrations in 10 children (aged 2.5-16 years) undergoing chemotherapy for either neuroblastoma or Ewing's tumour. To assess whether a simpler and less expensive nitrobenzylpyridine (NBP) spectrophotometric assay for alkylating activity was a satisfactory alternative to high-pressure liquid chromatography (HPLC), the plasma melphalan concentration was estimated by both methods in five cases. Analysis of the disposition of melphalan gave a mean half-life of 1.3 +/- 1.0 (SD) h, clearance 18.4 +/- 9.4 l X h-1 X m-2, and apparent volume of distribution 26.3 +/- 18.0 l X m-2. These pharmacokinetic parameters were similar to those found in adults: no correlation was found between any parameter and age or glomerular filtration rate. NBP alkylating activity determinations yielded consistent results and good correlation with plasma melphalan concentration. However, concordance analysis indicated a consistent bias, the NBP assay always giving lower estimates of plasma melphalan concentration: HPLC assay therefore remains the method of choice for determining plasma melphalan pharmacokinetics.